scholarly journals α-Synuclein oligomers in skin biopsy of idiopathic and monozygotic twin patients with Parkinson’s disease

Brain ◽  
2020 ◽  
Vol 143 (3) ◽  
pp. 920-931 ◽  
Author(s):  
Samanta Mazzetti ◽  
Milo J Basellini ◽  
Valentina Ferri ◽  
Erica Cassani ◽  
Emanuele Cereda ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Genetic Predisposition ◽  
Healthy Subjects ◽  
Proximity Ligation Assay ◽  
Healthy Controls ◽  
Proximity Ligation ◽  
Synaptic Terminals

Abstract A variety of cellular processes, including vesicle clustering in the presynaptic compartment, are impaired in Parkinson’s disease and have been closely associated with α-synuclein oligomerization. Emerging evidence proves the existence of α-synuclein-related pathology in the peripheral nervous system, even though the presence of α-synuclein oligomers in situ in living patients remains poorly investigated. In this case-control study, we show previously undetected α-synuclein oligomers within synaptic terminals of autonomic fibres in skin biopsies by means of the proximity ligation assay and propose a procedure for their quantification (proximity ligation assay score). Our study revealed a significant increase in α-synuclein oligomers in consecutive patients with Parkinson’s disease compared to consecutive healthy controls (P < 0.001). Proximity ligation assay score (threshold value > 96 using receiver operating characteristic) was found to have good sensitivity, specificity and positive predictive value (82%, 86% and 89%, respectively). Furthermore, to disclose the role of putative genetic predisposition in Parkinson’s disease aetiology, we evaluated the differential accumulation of oligomers in a unique cohort of 19 monozygotic twins discordant for Parkinson’s disease. The significant difference between patients and healthy subjects was confirmed in twins. Intriguingly, although no difference in median values was detected between consecutive healthy controls and healthy twins, the prevalence of healthy subjects positive for proximity ligation assay score was significantly greater in twins than in the consecutive cohort (47% versus 14%, P = 0.019). This suggests that genetic predisposition is important, but not sufficient, in the aetiology of the disease and strengthens the contribution of environmental factors. In conclusion, our data provide evidence that α-synuclein oligomers accumulate within synaptic terminals of autonomic fibres of the skin in Parkinson’s disease for the first time. This finding endorses the hypothesis that α-synuclein oligomers could be used as a reliable diagnostic biomarker for Parkinson’s disease. It also offers novel insights into the physiological and pathological roles of α-synuclein in the peripheral nervous system.

scholarly journals The Rotenone Models Reproducing Central and Peripheral Features of Parkinson’s Disease

NeuroSci ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 1-14
Author(s):  
Ikuko Miyazaki ◽  
Masato Asanuma
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Neurodegenerative Disorder ◽  
Rem Sleep Behavior Disorder ◽  
Experimental Models ◽  
Motor Symptoms ◽  
Sleep Behavior ◽  
Disease Modifying Drugs

Parkinson’s disease (PD) is a complex, multi-system, neurodegenerative disorder; PD patients exhibit motor symptoms (such as akinesia/bradykinesia, tremor, rigidity, and postural instability) due to a loss of nigrostriatal dopaminergic neurons, and non-motor symptoms such as hyposmia, autonomic disturbance, depression, and REM sleep behavior disorder (RBD), which precedes motor symptoms. Pathologically, α-synuclein deposition is observed in the central and peripheral nervous system of sporadic PD patients. To clarify the mechanism of neurodegeneration in PD and to develop treatment to slow or stop PD progression, there is a great need for experimental models which reproduce neurological features of PD. Animal models exposed to rotenone, a commonly used pesticide, have received most attention since Greenamyre and his colleagues reported that chronic exposure to rotenone could reproduce the anatomical, neurochemical, behavioral, and neuropathological features of PD. In addition, recent studies demonstrated that rotenone induced neuropathological change not only in the central nervous system but also in the peripheral nervous system in animals. In this article, we review rotenone models especially focused on reproducibility of central and peripheral multiple features of PD. This review also highlights utility of rotenone models for investigation of PD pathogenesis and development of disease-modifying drugs for PD in future.

scholarly journals Peripheral nervous system involvement in Parkinson's disease: Evidence and controversies

2014 ◽  
Vol 20 (12) ◽  
pp. 1329-1334 ◽  
Author(s):  
C. Comi ◽  
L. Magistrelli ◽  
G.D. Oggioni ◽  
M. Carecchio ◽  
T. Fleetwood ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
System Involvement

Lack of central and peripheral nervous system synuclein pathology in R1441G LRRK2-associated Parkinson’s disease

2018 ◽  
Vol 90 (7) ◽  
pp. 832-833 ◽  
Author(s):  
Dolores Vilas ◽  
Ellen Gelpi ◽  
Iban Aldecoa ◽  
Oriol Grau ◽  
Roberta Rodriguez-Diehl ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Peripheral Nervous System

scholarly journals Expression Profiling of Blood microRNAs 885, 361, and 17 in the Patients with the Parkinson’s disease: Integrating Interaction Data to Uncover the Possible Triggering Age-Related Mechanisms

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Molood Behbahanipour ◽  
Maryam Peymani ◽  
Mehri Salari ◽  
Motahare-Sadat Hashemi ◽  
Mohammad Hossein Nasr-Esfahani ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Severity ◽  
Cellular Senescence ◽  
Healthy Subjects ◽  
Target Genes ◽  
Healthy Controls ◽  
Early Stages ◽  
Age Related ◽  
Advanced Stages

Abstract MicroRNAs (miRNAs) have been reported to contribute to the pathophysiology of the Parkinson’s disease (PD), an age related-neurodegenerative disorder. The aim of present study was to compare the expression profiles of a new set of candidate miRNAs related to aging and cellular senescence in peripheral blood mononuclear cells (PBMCs) obtained from the PD patients with healthy controls and then in the early and advanced stages of the PD patients with their controls to clarify whether their expression was correlated with the disease severity. We have also proposed a consensus-based strategy to interpret the miRNAs expression data to gain a better insight into the molecular regulatory alterations during the incidence of PD. We evaluated the miRNA expression levels in the PBMCs obtained from 36 patients with PD and 16 healthy controls by the reverse transcription-quantitative real-time PCR and their performance to discriminate the PD patients from the healthy subjects assessed using the receiver operating characteristic curve analysis. Also, we applied our consensus and integration approach to construct a deregulated miRNA-based network in PD with the respective targets and transcription factors, and the enriched gene ontology and pathways using the enrichment analysis approach were obtained. There was a significant overexpression of miR-885 and miR-17 and the downregulation of miR-361 in the PD patients compared to the controls. The blood expression of miR-885 and miR-17 tended to increase along with the disease severity. On the other hand, the lower levels of miR-361 in the early stages of the PD patients, as compared to controls, and its higher levels in the advanced stages of PD patients, as compared to the early stages of the PD patients, were observed. Combination of all three miRNAs showed an appropriate value of AUC (0.985) to discriminate the PD patients from the healthy subjects. Also, the deregulated miRNAs were linked to the known PD pathways and the candidate related target genes were presented. We revealed 3 candidate biomarkers related to aging and cellular senescence for the first time in the patients with PD. Our in-silico analysis identified candidate target genes and TFs, including those related to neurodegeneration and PD. Overall, our findings provided novel insights into the probable age-regulatory mechanisms underlying PD and a rationale to further clarify the role of the identified miRNAs in the PD pathogenesis.

Accuracy and Reliability of Onset Detection Algorithms in Gait Initiation for Healthy Controls and Participants With Parkinson’s Disease

2019 ◽  
Vol 35 (6) ◽  
pp. 393-400
Author(s):  
Aisha Chen ◽  
Sandhya Selvaraj ◽  
Vennila Krishnan ◽  
Shadnaz Asgari
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Healthy Subjects ◽  
Center Of Pressure ◽  
Intraclass Correlation ◽  
Gait Initiation ◽  
Healthy Controls ◽  
Onset Detection ◽  
Detection Algorithms ◽  
Absolute Reliability

Accurate and reliable detection of the onset of gait initiation is essential for the correct assessment of gait. Thus, this study was aimed at evaluation of the reliability and accuracy of 3 different center of pressure–based gait onset detection algorithms: A displacement baseline–based algorithm (method 1), a velocity baseline–based algorithm (method 2), and a velocity extrema–based algorithm (method 3). The center of pressure signal was obtained during 10 gait initiation trials from 16 healthy participants and 3 participants with Parkinson’s disease. Intrasession and absolute reliability of each algorithm was assessed using the intraclass correlation coefficient and the coefficient of variation of center of pressure displacement during the postural phase of gait initiation. The accuracy was evaluated using the time error of the detected onset by each algorithm relative to that of visual inspection. The authors’ results revealed that although all 3 algorithms had high to very high intrasession reliabilities in both healthy subjects and subjects with Parkinson’s disease, methods 2 and 3 showed significantly better absolute reliability than method 1 in healthy controls (P = .001). Furthermore, method 2 outperformed the other 2 algorithms in both healthy subjects and subjects with Parkinson’s disease with an overall accuracy of 0.80. Based on these results, the authors recommend using method 2 for accurate and reliable gait onset detection.

Influence of Thoracoabdominal Movement on Pulmonary Function in Patients with Parkinson's Disease: Comparison with Healthy Subjects

2000 ◽  
Vol 14 (1) ◽  
pp. 43-47 ◽  
Author(s):  
Akira Tamaki ◽  
Yoshimi Matsuo ◽  
Takehiko Yanagihara ◽  
Kazuo Abe
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pulmonary Function ◽  
Forced Vital Capacity ◽  
Healthy Subjects ◽  
Vital Capacity ◽  
Healthy Controls ◽  
Pulmonary Dysfunction ◽  
Average Volume ◽  
Abdominal Movement

Patients with Parkinson's disease (PD) may develop pulmonary dysfunction, but the pathogenesis remains unclear. We investigated a correlation between thoracoab dominal movements and pulmonary function in seven patients with PD and 14 healthy controls. We measured vital capacity (VC) and forced vital capacity (FVC) using an autospirometer, and measured chest and abdominal movements using a respiraory in ductance plethysmography by fixing transducers on the rib cage and umbilicus. Pa tients with PD had significantly decreased % VC (90.3 ± 17.1 vs 105.8 ± 13.9%), chest movement (271.3 ± 79.6 vs. 375.2 ± 126.7% VT) and abdominal movement (217.6 ± 93.5 vs. 247.4 ± 100.2% VT) with 100% VT being an average volume of chest and abdomen at rest during measurement of VC. Patients with PD also had sig nificantly decreased % FVC (74.4 ± 20.6 vs. 97.6 ± 14.1%), chest movement (246.2 ± 115.2 vs. 344.5 ± 126.4% VT) and abdominal movement (160.3 ± 105.6 vs 207.6 ± 104.7% VT) with 100% VT being an average volume of chest and abdomen at rest during forced maximal inspiration. Based on the results, we conclude that a reduction of % VC in patients with PD correlated with chest movements, while a reduction of % FVC correlated with ab dominal movement in patients with PD.

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